Variant rs142289318 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017433.5(MYO3A):c.1796G>A(p.Ser599Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MYO3A
NM_017433.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.90

Variant links:

Genes affected

MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

MYO3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5 linkuse as main transcript	c.1796G>A	p.Ser599Asn	missense_variant	18/35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 linkuse as main transcript	c.1796G>A	p.Ser599Asn	missense_variant	18/35		NM_017433.5	ENSP00000495965	P1	Q8NEV4-1
MYO3A	ENST00000543632.5 linkuse as main transcript	c.1776+24013G>A		intron_variant		1		ENSP00000445909
MYO3A	ENST00000642197.1 linkuse as main transcript	n.2000G>A		non_coding_transcript_exon_variant	18/27
MYO3A	ENST00000647478.1 linkuse as main transcript	c.1777-4703G>A		intron_variant, NMD_transcript_variant				ENSP00000493932

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251180

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.3

.;N

REVEL

Uncertain

0.47

Sift

Benign

0.11

.;T

Sift4G

Benign

0.35

.;T

Polyphen

0.97

D;D

Vest4

0.44

MutPred

0.55

Loss of catalytic residue at S599 (P = 0.0968);Loss of catalytic residue at S599 (P = 0.0968);

MVP

0.94

MPC

0.12

ClinPred

0.83

GERP RS

6.0

Varity_R

0.48

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over